Is RD3 p.Ser5fs (c.13_14del) pathogenic?

RD3 p.Ser5fs (c.1314del) is classified Pathogenic/Likely pathogenic in RD3 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-01-07). Ultra-rare (popmax 0.0197%, mid); Associated with RD3-related disorder.

What condition is associated with RD3 p.Ser5fs (c.13_14del)?

RD3 p.Ser5fs (c.13_14del) is associated with RD3-related disorder, Leber congenital amaurosis 12 (ClinVar).

How common is RD3 p.Ser5fs (c.13_14del) in the general population?

RD3 p.Ser5fs (c.13_14del) is ultra-rare (popmax 0.0197%, mid) (gnomAD).

RD3 p.Ser5fs

c.13_14del · rs761112550 · VCV1458859

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0197%, mid)

Conditions

RD3-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 2 of 3
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -10	GERP -4
Overall
CADD	29.2	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0197% Middle Eastern · 1/5,086 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.00031% 5/1,611,836 alleles · ultra-rare exomes 3/1,459,656 · genomes 2/152,180 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0197%	5,086
European (non-Finnish)	0.000339%	294,788

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: RD3
Protein: p.Ser5fs
Coding: c.13_14del
MANE Select: NM_001164688
dbSNP: rs761112550
Type: Microsatellite
Location: chr1:211481402 (GRCh38)
Gene constraint: LOEUF 1.116 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.99 · 1 PDB

Full RD3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

RD3-related disorder

Also linked: Leber congenital amaurosis 12

Similar variants

RD3 c.296+1G>T Pathogenic/Likely pathogenic ★★ same condition
RD3 p.Arg38Ter Pathogenic ★★ same condition
RD3 p.Tyr60Ter Pathogenic ★★ same condition
RD3 c.-572G>A Uncertain significance ★★ same condition
RD3 c.*1277G>A Uncertain significance ★★ same condition
RD3 p.Ala135Val Uncertain significance ★★ ⚠ same condition
RD3 p.Arg15Trp Uncertain significance ★★ ⚠ same condition
RD3 p.Arg182Gln Uncertain significance ★★ ⚠ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/rd3-p-ser5fs (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown